PHARMACODYNAMICS OF MK-0963, A NEW 5-ALPHA-REDUCTASE INHIBITOR - EFFECTS ON SERUM ANDROGEN CONCENTRATIONS

The hormonal effects after a 10-day administration of a 4-azasteroid i nhibitor of 5 alpha-reductase, MK-0963 previously L-654,066), were eva luated in 35 healthy male volunteers in an increasing-dose, five-panel design. Marked suppression of serum dihydrotestosterone was observed after the once-daily administration at each active dose level (placebo , 0.1, 0.5, 1.0, 10, and 25 mg). Maximum dihydrotestosterone suppressi on occurred at doses greater than or equal to 10 mg. The mean percenta ge (+/- SE) decreases in dihydrotestosterone at 24 hours after the las t dose in the groups treated with the 10 and 25 mg doses were 78% +/- 4.9% and 80% +/- 2.9%, respectively. The 25 mg dose maintained a dihyd rotestosterone suppression of at least 70% for more than 6 days after the last dose. No consistent changes in serum testosterone were noted. This study shows that administration of multiple doses of MK-0963 res ults in a substantial suppression of serum dihydrotestosterone with no consistent influence on serum testosterone concentrations.